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Protein

Proteinase-activated receptor 4

Gene

F2RL3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.1 Publication

GO - Molecular functioni

  • G-protein coupled receptor activity Source: GO_Central
  • thrombin-activated receptor activity Source: ProtInc

GO - Biological processi

  • blood coagulation Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: Reactome
  • phospholipase C-activating G-protein coupled receptor signaling pathway Source: ProtInc
  • platelet activation Source: Reactome
  • platelet dense granule organization Source: BHF-UCL
  • positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Source: GO_Central
  • positive regulation of release of sequestered calcium ion into cytosol Source: BHF-UCL
  • positive regulation of Rho protein signal transduction Source: GO_Central
  • response to wounding Source: ProtInc
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processBlood coagulation, Hemostasis

Enzyme and pathway databases

ReactomeiR-HSA-375276 Peptide ligand-binding receptors
R-HSA-416476 G alpha (q) signalling events
R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs)
SIGNORiQ96RI0

Names & Taxonomyi

Protein namesi
Recommended name:
Proteinase-activated receptor 4
Short name:
PAR-4
Alternative name(s):
Coagulation factor II receptor-like 3
Thrombin receptor-like 3
Gene namesi
Name:F2RL3
Synonyms:PAR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000127533.3
HGNCiHGNC:3540 F2RL3
MIMi602779 gene
neXtProtiNX_Q96RI0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini48 – 82ExtracellularSequence analysisAdd BLAST35
Transmembranei83 – 103Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini104 – 108CytoplasmicSequence analysis5
Transmembranei109 – 129Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini130 – 151ExtracellularSequence analysisAdd BLAST22
Transmembranei152 – 172Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini173 – 192CytoplasmicSequence analysisAdd BLAST20
Transmembranei193 – 213Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini214 – 247ExtracellularSequence analysisAdd BLAST34
Transmembranei248 – 268Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini269 – 283CytoplasmicSequence analysisAdd BLAST15
Transmembranei284 – 304Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini305 – 319ExtracellularSequence analysisAdd BLAST15
Transmembranei320 – 343Helical; Name=7Sequence analysisAdd BLAST24
Topological domaini344 – 385CytoplasmicSequence analysisAdd BLAST42

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi47R → A: No proteolytic cleavage (by thrombin or trypsin). 1 Publication1
Mutagenesisi68R → A: No effect on receptor activation. 1 Publication1

Organism-specific databases

DisGeNETi9002
OpenTargetsiENSG00000127533
PharmGKBiPA27949

Chemistry databases

ChEMBLiCHEMBL4691
GuidetoPHARMACOLOGYi350

Polymorphism and mutation databases

BioMutaiF2RL3
DMDMi116242700

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
PropeptideiPRO_000001276218 – 47Removed for receptor activationBy similarityAdd BLAST30
ChainiPRO_000001276348 – 385Proteinase-activated receptor 4Add BLAST338

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi56N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi149 ↔ 228PROSITE-ProRule annotation

Post-translational modificationi

A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei47 – 48Cleavage; by thrombin or trypsinBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ96RI0
PeptideAtlasiQ96RI0
PRIDEiQ96RI0

PTM databases

iPTMnetiQ96RI0
PhosphoSitePlusiQ96RI0

Miscellaneous databases

PMAP-CutDBiQ96RI0

Expressioni

Tissue specificityi

Widely expressed, with highest levels in lung, pancreas, thyroid, testis and small intestine. Not expressed in brain, kidney, spinal cord and peripheral blood leukocytes. Also detected in platelets.

Gene expression databases

BgeeiENSG00000127533
CleanExiHS_F2RL3
ExpressionAtlasiQ96RI0 baseline and differential

Interactioni

Protein-protein interaction databases

BioGridi1144811 interactor.
ELMiQ96RI0
STRINGi9606.ENSP00000248076

Chemistry databases

BindingDBiQ96RI0

Structurei

Secondary structure

1385
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi44 – 46Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZPKX-ray1.80P/Q46-53[»]
3QDZX-ray2.80E/F39-47[»]
ProteinModelPortaliQ96RI0
SMRiQ96RI0
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96RI0

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi301 – 305Poly-Leu5

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFSN Eukaryota
ENOG410YD35 LUCA
GeneTreeiENSGT00910000143980
HOGENOMiHOG000116291
HOVERGENiHBG096365
InParanoidiQ96RI0
KOiK04236
OMAiPFVYYYV
OrthoDBiEOG091G0C2F
PhylomeDBiQ96RI0
TreeFamiTF350010

Family and domain databases

CDDicd15372 7tmA_PAR4, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR003944 Prot_act_rcpt_4
IPR003912 Protea_act_rcpt
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR01428 PROTEASEAR
PR01430 PROTEASEAR4
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q96RI0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWGRLLLWPL VLGFSLSGGT QTPSVYDESG STGGGDDSTP SILPAPRGYP
60 70 80 90 100
GQVCANDSDT LELPDSSRAL LLGWVPTRLV PALYGLVLVV GLPANGLALW
110 120 130 140 150
VLATQAPRLP STMLLMNLAA ADLLLALALP PRIAYHLRGQ RWPFGEAACR
160 170 180 190 200
LATAALYGHM YGSVLLLAAV SLDRYLALVH PLRARALRGR RLALGLCMAA
210 220 230 240 250
WLMAAALALP LTLQRQTFRL ARSDRVLCHD ALPLDAQASH WQPAFTCLAL
260 270 280 290 300
LGCFLPLLAM LLCYGATLHT LAASGRRYGH ALRLTAVVLA SAVAFFVPSN
310 320 330 340 350
LLLLLHYSDP SPSAWGNLYG AYVPSLALST LNSCVDPFIY YYVSAEFRDK
360 370 380
VRAGLFQRSP GDTVASKASA EGGSRGMGTH SSLLQ
Length:385
Mass (Da):41,133
Last modified:October 17, 2006 - v3
Checksum:iFACE32F10D5C561E
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_028300120A → T3 PublicationsCorresponds to variant dbSNP:rs773902Ensembl.1
Natural variantiVAR_028301215R → Q. Corresponds to variant dbSNP:rs2230799Ensembl.1
Natural variantiVAR_012852296F → V1 PublicationCorresponds to variant dbSNP:rs2227346Ensembl.1
Natural variantiVAR_012853310P → L1 PublicationCorresponds to variant dbSNP:rs2227376Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF080214 mRNA Translation: AAC28860.1
AF055917 mRNA Translation: AAC25699.1
AY431102 mRNA Translation: AAR08487.1
AF384819 Genomic DNA Translation: AAK61908.1
BC074782 mRNA Translation: AAH74782.2
CCDSiCCDS12350.1
RefSeqiNP_003941.2, NM_003950.3
UniGeneiHs.137574

Genome annotation databases

EnsembliENST00000248076; ENSP00000248076; ENSG00000127533
GeneIDi9002
KEGGihsa:9002
UCSCiuc002nfa.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPAR4_HUMAN
AccessioniPrimary (citable) accession number: Q96RI0
Secondary accession number(s): O76067, Q6DK42
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: October 17, 2006
Last modified: February 28, 2018
This is version 154 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome